BIOLOGICAL ACTIVITIES OF OPTICAL ISOMERS OF 6-CHLORO-5-CYCLOHEXYLIN DAN-1-CARBOXYLIC ACID (TAI-284: ANTI-INFLAMMATORY AGENT)

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A potent anti-inflammatory compound, TAI-284, and its optical isomers were subjected to the pharmacological, toxicological and metabolic studies in rats, mice and guinea-pigs. In anti-inflammatory, analgesic and antipyretic activities examined in rats and mice, the d-isomer was the most potent, followed by the racemate, and the l-isomer was the lowest. Similar results were obtained regarding toxicity and ulcerogenicity. The d-isomer maintained the highest plasma level, followed in decreasing order by the racemate and the l-isomer, when they were administered orally to rats. In the same experiment, the plasma level of the l-isomer's metabolites was the highest, followed in decreasing order by that of the racemate's metabolites and that of the disomer's metabolites. In Vitro, the l-isomer was most rapidly transformed into the metabolites while the d-isomer was most slowly transformed. On the other hand, the d-isomer was as potent as the l-isomer in the anti-inflammatory activity in guineapigs. In this species TAI-284 is hardly biotransformed into the metabolites. It is postulated that the rate of biotransformation of these compounds has a great influence on their pharmacological activities.
公益社団法人日本薬理学会の論文